Saussurea lappa extract suppresses TPA-induced cell invasion via inhibition of NF-κB-dependent MMP-9 expression in MCF-7 breast cancer cells.

BACKGROUND: Saussurea lappa (SL) has been used as a traditional herbal medicine to treat abdominal pain and tenesmus, and has been suggested to possess various biological activities, including anti-tumor, anti-ulcer, anti-inflammatory, anti-viral, and cardiotonic activities. The effect of SL on breast cancer metastasis, however, is unknown. Cell migration and invasion are crucial in neoplastic metastasis. Matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix, is a major component in cancer cell invasion. METHODS: Cell viability was examined by MTT assay, whereas cell motility was measured by invasion assay. Western blot, Real-time PCR, and Zymography assays were used to investigate the inhibitory effects of ESL on matrix metalloproteinase-9 (MMP-9) expression level in MCF-7 cells. EMSA confirmed the inhibitory effects of ESL on DNA binding of NF- κB in MCF-7 cells. RESULTS: Cells threated with various concentrations of Saussurea lappa (ESL) for 24 h. Concentrations of 2 or 4 µM did not lead to a significant change in cell viability or morphology. Therefore, subsequent experiments utilized the optimal non-toxic concentration (2 or 4 µM) of ESL. In this study, we investigated the inhibitory effect of ethanol extract of ESL on MMP-9 expression and cell invasion in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MCF-7 cells. ESL inhibited the TPA-induced transcriptional activation of nuclear factor-kappa B (NF-κB). However, this result obtained that ESL did not block the TPA-induced phosphorylation of the kinases: p38, ERK, and JNK. Therefore, ELS-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of NF-kB pathway in MCF-7 cells. CONCLUSIONS: These results indicate that ELS-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of NF-kB pathway in MCF-7 cells. Thus, ESL has potential for controlling breast cancer invasiveness in vitro.

Elucidating the mechanisms of post-stroke motor recovery mediated by electroacupuncture using diffusion tensor tractography.

Acupuncture has been commonly used for post-stroke patients, and electroacupuncture allows simultaneous application of acupuncture and electrical stimulation. We aimed to elucidate the mechanism of electroacupuncture on post-stroke motor recovery using diffusion tensor tractography. A total of 33 subacute stroke patients were recruited. The control group was subjected to conventional rehabilitation therapy. In contrast, the patients in the experimental group received electroacupuncture treatment for 30 min per session for 4 weeks in addition to the rehabilitation therapy. Fugl-Meyer assessment of the lower extremity (FMA_L), functional ambulation categories (FAC), and the Korean version of modified Barthel index (K-MBI) were used to compare behavioral outcomes between groups. The corticospinal tract (CST) was examined before and after the intervention via diffusion tensor tractography (DTT) to determine the motor recovery mechanism mediated by electroacupuncture. After 4 weeks of intervention, both the control and experimental groups showed a significant improvement with respect to FMA_L, FAC, and K-MBI. The level of improvement in FMA_L, FAC, and K-MBI did not vary significantly between the two groups. However, DTT results showed that the CST fractional anisotropy of the affected side (control: from 0.456 to 0.464, experimental: from 0.459 to 0.512) and its ratio (control: from 89.8 to 90.3, experimental: from 90.2 to 93.3) were significantly different between the two groups (p = 0.032 and p = 0.018). In addition, there were significant differences in the CST axial diffusivity of affected side (control: from 0.783 to 0.877, experimental: from 0.840 to 0.897) and its ratio variation (control: from 87.9 to 100.0, experimental: from 95.7 to 100.7) between the groups (p = 0.003 and p = 0.001). Electroacupuncture played a role in promoting brain plasticity and delaying neural degeneration in subacute period after stroke. Thus, electroacupuncture could be an effective adjuvant therapy in addition to conventional rehabilitation for motor recovery after stroke in a long-term perspective.

Acupuncture and electroacupuncture for stroke: A protocol for overview of systematic review and meta-analysis.

BACKGROUND: The aim of this study was to undertake a systematic overview of meta-analyses and published systematic reviews to identify whether and when acupunctureand electroacupuncture are deemed efficacious treatment options for stroke and stroke-related disorders. METHODS: Four databases, namely, PubMed, AMED, EMBASE, and the Cochrane Library will be searched from their inception. Two reviewers will independently perform study selection, data extraction, and assessment. This will be followed by an assessment of the methodological and report quality using the Assessment of Multiple Systematic Reviews-2 tool. Finally, the study will entail the assessment of evidence quality by employing the Grading of Recommendations Assessment, Development, and Evaluation system. RESULTS: This overview is expected to provide data on using acupuncture for stroke and stroke-related disorders on the basis of the included systematic reviews' qualitative and quantitative syntheses. CONCLUSION: This overview will assess the benefits as well as hazards of acupuncture for stroke, subsequently providing patients and practitioners with useful information and have implications for future studies on the topic. TRIAL REGISTRATION NUMBER: Reviewregistry1263.

Sasim attenuates LPS-induced TNF-alpha production through the induction of HO-1 in THP-1 differentiated macrophage-like cells.

AIM OF THE STUDY: Sasim, a traditional prescription composed of seven herbal mixtures, has been widely used as an oriental medicine for the treatment of cerebral infarction in Korea. However, the regulatory mechanisms by which the formula affects immune processing in cerebral infarction patients remain unknown. MATERIALS AND METHODS: The levels of secretory protein of tumor necrosis factor (TNF)-alpha were determined in both THP-1 differentiated macrophage-like (THP-1/M) cells and Peripheral blood mononuclear cells (PBMCs) from cerebral infarction patients. Also, the levels of protein and mRNA of TNF-alpha and heme oxygenase-1 (HO-1) were detected in THP-1/M cells under our experimental condition. RESULTS: Sasim markedly suppressed lipopolysaccharide (LPS)-induced TNF-alpha at the levels of secretory protein and mRNA in both PBMCs from cerebral infarction patients and THP-1/M cells. Interestingly, Sasim strongly induced HO-1, the rate-limiting enzyme of heme catabolism, at both the protein and mRNA levels in THP-1/M cells. Treatment with tin protoporphyrin IX (SnPP), an inhibitor of the catalytic activity of HO, significantly abolished the suppressive effect of Sasim on LPS-induced TNF-a production in THP-1/M cells. CONCLUSIONS: These data indicate that Sasim may be beneficial in the cessation of inflammatory processes associated with cerebral infarction through the induction of HO-1 expression.

Antiinflammatory effect of Daesiho, a Korean traditional prescription for cerebral infarct patients.

Daesiho, a prescription composed of eight herbal mixtures, has been widely used in the treatment of cerebral infarct in Oriental medicine. However, the mechanisms by which the formula affects the production of pro-inflammatory cytokines in cerebral infarct patients remains unknown. The levels of secretory protein pro-inflammatory cytokines, including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6, were significantly increased in both lipopolysaccharide (LPS) and phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) from cerebral infarct patients and LPS-stimulated THP-1 differentiated macrophage-like cells (THP-1/M). However, pretreatment with Daesiho significantly inhibited the secretion of pro-inflammatory cytokines, including TNF-alpha, IL-1beta, and IL-6, in stimulated PBMCs and THP-1/M cells. In addition, Daesiho significantly suppressed mRNA expression of pro-inflammatory cytokines. Therefore, these data indicate that Daesiho may be beneficial in the cessation of inflammatory processes of cerebral infarction through suppression of the production of pro-inflammatory cytokines via inhibition of mRNA expression.

Anti-inflammatory effect of So-Pung-Tang, a Korean traditional prescription for cerebral infarction patients.

So-Pung-Tang (Sopung), a prescription composed of 14 herbal mixtures, has been widely used in the treatment of cerebral infarction in Oriental Medicine. However, the mechanisms by which the formula affects on the production of pro-inflammatory cytokines in cerebral infarction patients remain unknown yet. The levels of secretory protein of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-alpha, interlukin (IL)-1beta, and IL-6, were significantly increased in both THP-1 differentiated macrophage-like cells (THP-1/M) and peripheral blood mononuclear cells (PBMCs) from cerebral infarction patients after stimulation. However, pretreatment with Sopung markedly inhibited the secretion of TNF-alpha and IL-6, but not IL-1beta, in lipopolysaccharide (LPS)-stimulated THP-1/M cells and PBMCs treated with LPS and phytohemagglutinin (PHA). Furthermore, Sopung significantly inhibited LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK1/2) and c-jun N-terminal kinase (JNK), but not p38 in THP-1/M cells. These data indicate that Sopung may be beneficial in the cessation of inflammatory processes of cerebral infarction through suppression of ERK1/2 and JNK activation.

Anti-inflammatory effect of Sasim extracts in PHA-stimulated THP-1 and peripheral blood mononuclear cells from cerebral infarction patients.

Sasim, a prescription composed of seven herbal mixtures, has been widely used for the treatment of cerebral infarction as an oriental medicine in Korea. However, the mechanisms by which the formula affects on the production of pro-inflammatory cytokines in cerebral infarct patients remain unknown yet. The levels of secretory protein and mRNA of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-alpha, interlukin (IL)-1beta, and IL-6, were significantly increased in both THP-1 differentiated macrophage-like cells (T/M) and peripheral blood mononuclear cells (PBMCs) from cerebral infarct patients at 24h after stimulation with phytohemagglutinin (PHA) (p<0.05). However, pretreatment of Sasim strongly suppressed the secretion of pro-inflammatory cytokines in PHA-stimulated T/M cells and PBMCs. Moreover, Sasim significantly suppressed the transcriptional levels of pro-inflammatory cytokines in PHA-stimulated THP-1/M cells. These data indicate that Sasim may be beneficial in the cessation of inflammatory processes of cerebral infarction through suppression on the production of pro-inflammatory cytokines via inhibition of mRNA expression.

Anti-inflammatory effect of dohongsamultang through inhibition of nuclear factor-kappaB activation in peripheral blood mononuclear cells of patients with cerebral infarction.

The Korean indigenous medicine "Dohongsamultang (DHSMT)" has long been used for various cerebrovascular diseases. However, the exact mechanism for the anti-inflammatory effect of DHSMT is not completely understood. The aim of the present study is to elucidate how DHSMT modulates the inflammatory reaction in lipopolysaccaride (LPS)-stimulated peripheral mononuclear cells from cerebral infarction (CI) patients. Production and expression of cytokine was measured via the ELISA and RT-PCR methods. The level of nuclear factor-kappa B (NF-kappaB)/Rel A protein and NF-kappaB DNA binding activity were determined via the Western blot analysis and transcription factor enzyme-linked immunoassay. It showed that DHSMT inhibited the production of TNF-alpha, IL-1beta, and IL-6 induced by LPS in a dose-dependent manner (p < 0.05). The maximal inhibition rates for TNF-alpha, IL-1beta, and IL-6 production by DHSMT were about 50.18%, 32.13%, and 38.03%, respectively. DHSMT inhibited the TNF-alpha mRNA expression in a dose-dependent manner. We also showed that the inhibitory effect of DHSMT is through the suppression of the NF-kappaB pathway. The study suggests an important molecular mechanism by GMGHT to reduce inflammation, which might explain its beneficial effect in the regulation of inflammatory reactions.

Samul extract protects against the H2O2-induced apoptosis of H9c2 cardiomyoblasts via activation of extracellular regulated kinases (Erk) 1/2.

Samul extract, containing Radix Rehmanniae, Radix Angelicae Gigantis, Radix Paeoniae, and Rhizoma Cnidii, has been traditionally used for treatment of ischemic heart and brain damages in Oriental medicine. However, little is known about the mechanism by which Samul rescues cells from cytotoxic damage. This study was designed to investigate the protective mechanisms of Samul on H(2)O(2)-induced death of H9c2 cells. Treatment with H(2)O(2) markedly decreased the viability of H9c2 cells in a dose- and time-dependent manner, which was significantly prevented by pre-treatment with Samul. The nature of death of H9c2 cells by H(2)O(2) was demonstrated by apoptotic features, including ladder-pattern fragmentation of genomic DNA and chromatin condensation, which were markedly abolished by pretreatment of Samul in H(2)O(2)-treated cells. We further demonstrated that MEK inhibitor, PD98059, dose-dependently attenuated the protective effects of Samul against H(2)O(2), whereas inhibitors of Jnk and p38 did not. Consistently, Samul induced the early phosphorylation of Erk, p44, in H(2)O(2)-treated cells. In addition, treatment with Samul also resulted in an increase of expression of anti-apotogenic Bcl2 protein, which was decreased by H(2)O(2). However, it inhibited the expression of apotogenic Bax protein in H(2)O(2)-treated cells. Taken together, these results suggest that the protective effects of Samul against oxidative damage may be achieved via activation of MAP kinase, Erk as well as Bcl2 family proteins.

Zingansikpoongtang modulates beta-amyloid and IL-1beta-induced cytokine production and cyclooxygenase-2 expression in human astrocytoma cells U373MG.

Zingansikpoongtang (ZST) is a Korean herbal prescription, which has been successfully applied for the various neurodegenerative diseases. However, its effect remains unknown in the experimental models. In this study, we examined the effect of ZST on production of interleukin (IL)-6 and IL-8, and expression of cyclooxygenase (COX)-2 in IL-1beta and beta-amyloid [25-35] fragment (Abeta)-stimulated human astrocytoma cell line U373MG. We examined the biological effects of ZST in U373MG cells using MTT assay, enzyme-linked immunosorbent assay, and Western blotting. ZST alone had no effect on the cell viability. The production of IL-6 and IL-8 was dose-dependently inhibited by pretreatment with ZST (0.01-1 mg/ml) on IL-1beta and Abeta-stimulated U373MG cells. The expression level of COX-2 protein was up-regulated by IL-1beta and Abeta, but the increased level of COX-2 was partially down-regulated by pretreatment with ZST (1 mg/ml). These data indicate that ZST has a modulatory effect of cytokine production and COX-2 expression on IL-1beta and Abeta-stimulated U373MG cells, which might explain its beneficial effect in the treatment of various neurodegenerative diseases.

Quercetin protects the hydrogen peroxide-induced apoptosis via inhibition of mitochondrial dysfunction in H9c2 cardiomyoblast cells.

Quercetin possesses a broad range of pharmacological properties, including protection of LDL from oxidation. However, little is known about the mechanism by which quercetin rescues cardiomyoblasts from oxidative damage. This study was designed to investigate the protective mechanism of quercetin on H(2)O(2)-induced toxicity of H9c2 cardiomyoblasts. Oxidative stress, such as H(2)O(2), ZnCl(2), and menadione, significantly decreased the viability of H9c2 cells, which was accompanied with apparent apoptotic features, including fragmentation of genomic DNA as well as activation of caspase protease. However, quercetin markedly inhibited the apoptotic characteristics via reduction of intracellular reactive oxygen species generation. Also, it prevented the H(2)O(2)-mediated mitochondrial dysfunction, including disruption of mitochondria membrane permeability transition as well as an increase in expression of apoptogenic Bcl-2 proteins, Bcl-2 and Bcl-X(L). Furthermore, pretreatment of quercetin inhibited the activation of caspase-3, thereby both cleavage of poly(ADP-ribose) polymerase and degradation of inhibitor of caspase-activated DNase/DNA fragmentation factor by H(2)O(2) were completely abolished. Taken together, these data suggest that protective effects of quercetin against oxidative injuries of H9c2 cardiomyoblasts may be achieved via modulation of mitochondrial dysfunction and inhibition of caspase activity.

Polymorphism of angiotensin-converting enzyme, angiotensinogen, and apolipoprotein E genes in Korean patients with cerebral infarction.

The homozygous deletion allele of the angiotensin-converting enzyme gene (ACE/DD), homozygous threonine allele of the angiotensinogen gene (AGN/TT), and the epsilon4 allele of the apolipoprotein E gene (apoE/epsilon4) are reported to be associated with ischemic heart disease. Cerebral infarction (CI) is another atherosclerotic disease, and the effects of these polymorphisms on CI have been confusing. The frequency of the DD genotype of the ACE gene, but not the TT genotype of the AGN gene and the epsilon4 allele of ApoE, was significantly higher in subjects with than those without CI in Japan. In this study, we investigated whether ACE/DD, AGN/TT, and apoE/epsilon4 genotypes are associated with CI and whether genetic risk is enhanced by the effect of one upon another. We ascertained these genotypes in patients with CI (n = 365), diagnosed by brain computed tomography. Control subjects for the infarction group were randomly selected from 319 subjects matched for age, gender, and history of hypertension with patients. The ACE/DD genotype was not associated with CI. Frequency of the AGN/TT genotype was higher in patients with CI than in controls (chi2 = 12.287, p < 0.05). The frequency of t allele was 0.88 in patients and 0.82 in controls (chi2 = 11.041, p < 0.05; odds ratio, 1.7). Furthermore, the AGN/TT genotype increased the relative risk for CI in subjects with the ACE/DD genotype (chi2 = 7.8, p < 0.05; odds ratio, 1.9). There was no significant association between apoE/epsilon4 and CI. These results suggest that AGN/TT predicts CI and ACE/DD enhances the risk for CI associated with AGN/TT in a Korean population.

Genetic susceptibility to ischemic cerebrovascular disease in Koreans.

Ischemic cerebrovascular disease (ICVD) is a multifactorial disease caused by the interactions of several genetic and environmental factors. Tobacco smoke is a major cause of both cancer and vascular disease. Although its carcinogenic role via induction of DNA damage and mutation is well established, the mechanisms involved in vascular disease remain unclear. One possibility is that DNA damage causes smooth muscle cell proliferation in the intima of arteries, thereby contributing to atherothrombotic processes. The binding of chemicals to DNAis modulated by detoxification enzymes, including glutathione S-transferase (GST). We examined whether polymorphisms in this gene, as well as the angiotensin-converting enzyme (ACE) gene influence the risk of ICVD on smoking status. DNA was analyzed for deletions in the GST M1, T1, and ACE genes by polymerase chain reaction (PCR). No significant association was observed between GST null genotype and ICVD, even in smokers. However, a significant association between ACE and ICVD was observed only in smokers (chi(2) = 0.023, p < 0.05). We conclude that GST polymorphism is not a risk factor for the development of ICVD through smoking and suggest a high probability that ACE polymorphism may contribute to the odds of ICVD in smokers.

Association of interleukin-1 alpha gene polymorphism with cerebral infarction.

Interleukin-1 (IL-1) has pleiotropic actions in the central nervous system. During the last decade, a growing corpus of evidence has indicated an important role of this cytokine in the development of brain damage following cerebral ischemia. The expression of IL-1 in the brain is dramatically increased during the early and chronic stage of infarction. The IL-1 gene cluster on chromosome 2q14 contains three related genes (IL1alpha, IL1beta, and IL1 receptor antagonist) located within a 430-kb region. T and C alleles exist for the IL-1alpha-889 regulatory region and the TT genotype has been reported to increase the production of the protein in lipopolysaccharide (LPS)-stimulated mononuclear cells from IL-1alpha-889 TT carriers. We examined whether the IL-1alpha polymorphism affects the probability of cerebral infarction (CI). We genotyped 360 CI patients and 519 healthy controls for the same polymorphism. A significant increase was found for the IL-1alpha T allele in CI patients compared with controls (chi2=5.026, P=0.025). We conclude that the IL-1alpha-889 polymorphism is a major risk factor for CI in Koreans.

Differential regulation by Seogak Jihwang-Tang on cytokines production in peripheral blood mononuclear cells from the cerebral infarction patients presenting with altered consciousness.

Seogak Jihwang-Tang (SJT) has been widely used to treat patients suffering from cerebral infarction. However, very little scientific investigation has been carried out. We investigated the effect of SJT on the production of various cytokines using peripheral blood mononuclear cells from the cerebral infarction patients presenting with altered consciousness. The cytokines production was determined by enzyme-linked immunosorbent assay. The amount of IL-4, IL-10 and TGF-beta1 in culture supernatant significantly increased in the SJT, lipopolysaccharide (LPS) or PHA-treated cells compared to unstimulated cells (P < 0.05). We also showed that increased IL-4 and IL-10 levels by LPS or phytohaemagglutinin (PHA) were significantly inhibited by SJT in a dose-dependent manner. Maximal inhibition rate of IL-4 and IL-10 production by SJT was 45.6 +/- 3.3% and 61 +/- 4.7% for LPS-stimulated cells and 27.3 +/- 1.2% and 83.6 +/- 2% for PHA-stimulated cells, respectively (P < 0.05). On the other hand, SJT significantly increased the LPS or PHA-induced TGF-beta1 production (P < 0.05). These data suggest that SJT has a regulatory effect on the cytokines production, which might explain its beneficial effect in the treatment of cerebral infarction.

Anti-inflammatory effect of oyaksungisan in peripheral blood mononuclear cells from cerebral infarction patients.

Oyaksungisan, the herbal prescription composed of eleven herbs, has been widely used in treatment of cerebral infarct in Oriental Medicine. However, the mechanisms by which the herbal formula affects on the production of pro- and anti-inflammatory cytokines in cerebral infarction patients remain unknown yet. The secretory levels of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6, and IL-10 were significantly increased in both LPS and PHA-stimulated peripheral blood mononuclear cells (PBMCs) from cerebral infarction patients. However, pretreatment with oyaksungisan significantly inhibited the secretion of pro- and anti-inflammatory in PBMCs. Also, oyaksungisan induced a significant increase of transforming growth factor (TGF)-beta1 in PBMCs. Thus, these data indicate that oyaksungisan may be beneficial in the cessation of inflammatory processes of cerebral infarct through suppression of TNF-alpha, IL-1beta, IL-6, and IL-10 and induction of TGF-beta1.

Glutathione s-transferase gene polymorphism and ischemic cerebrovascular disease.

Glutathione S-transferase polymorphisms (GST) were examined in 142 cases with ischemic cerebrovascular disease (ICVD) to explore whether the GST polymorphisms confer a risk to an individual to develop ICVD. Tobacco smoke is a major cause of both cancer and vascular disease. The subjects were therefore stratified with ICVD for smoking status, and then the authors examined whether polymorphisms in this detoxification enzyme gene, GST, influence risk of ICVD. The GST genotype was analyzed by the polymerase chain reaction. Neither GSTM1 nor GSTT1 genotypes in the ICVD group was significantly different from the control group (n=344), even in smokers. The authors attempted the combined analysis for GSTM1 and GSTT1 genotypes in ICVD for smoking status. No significant association was observed among the combined genotypes and ICVD. The observations do not confirm the effect of the GSTM1 and GSTT1 genotypes as a risk factor for ICVD, even in smokers. However, this approach provides a way of addressing the hypothesis that environmental genotoxins could play a role in the etiopathogenesis of ICVD.

The anti-inflammatory effect of Gigukjiwhangwhangami through the inhibition of nuclear factor-kappaB activation in the peripheral blood mononuclear cells of patients with cerebral infarction.

The Korean genuine medicine "Gigukjiwhangwhangami (GJWGM)" has long been used for various cerebrovascular diseases. However, the exact mechanism that accounts for the anti-inflammatory effect of GJWGM is not completely understood. The aim of the present study is to elucidate how GJWGM modulates the inflammatory reaction in lipopolysaccaride (LPS)-stimulated peripheral mononuclear cells from patients with cerebral infarction. Production of cytokine was measured by the ELISA and RT-PCR method. The level of nuclear factor-kappaB (NF-kappaB)/Rel A protein and NF-kappaB DNA binding activity were determined by the Western blot analysis and TF-EIA method. We showed that GJWGM inhibited the production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1alpha, IL-6, and IL-8 induced by LPS in dose dependent manner (p<0.05). Maximal inhibition rate of TNF-alpha, IL-1beta, IL-6 and IL-8 production by GJWGM was about 54.34%, 41.37%, 44.04%, and 54.46%, respectively. GJWGM inhibited the TNF-alpha and IL-8 mRNA expression. In addition, we showed that the inhibitory mechanism of GJWGM is through the suppression of NF-kappaB pathway. Our study suggests that an important molecular mechanism by GJWGM reduce inflammation, which may explain its beneficial effect in the regulation of inflammatory reactions.

The effect of SHJKS on cytokines production and NF-kappaB activation in the peripheral blood mononuclear cells of patients with cerebral infarction.

The Korean genuine medicine "Seonghyangjeongkisan" (SHJKS) has long been used for various cerebrovascular diseases. However, very little scientific investigation has been carried out. Cytokines involved in the regulation of inflammatory reactions and immune responses may play a role in the pathogenesis of cerebral infarction (CI). The aim of the present study is to elucidate how SHJKS modulates the inflammatory reaction in lipopolysaccaride (LPS) plus phytohaemagglutinin (PHA)-stimulated peripheral mononuclear cells (PBMCs) from CI patients. The amount of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and IL-8 in PBMC culture supernatant was significantly increased in the LPS plus PHA treated cells compared to unstimulated cells. SHJKS inhibited the TNF-alpha, IL-1beta, IL-6, and IL-8 production in dose dependent manner. Maximal inhibition rate of the TNF-alpha, IL-1beta, IL-6, and IL-8 by SHJGS (1.0 mg/ml) was 68.01 +/- 0.28% (P < 0.01), 52.11 +/- 0.56 % (P < 0.01), 53.42 +/- 0.46 % (P < 0.01), and 46.70 +/- 0.37% (P < 0.05), respectively. In addition, we show that SHJKS suppressed nuclear factor (NF)-kappaB activation induced by LPS plus PHA, leading to suppression of IkappaB-alpha phosphorylation and degradation. These results suggest that SHJKS might have regulatory effects on LPS plus PHA-induced cytokine production and NF-kappaB activation, which might explain its beneficial effect in the treatment of CI.

Effect of Danchunwhangagam on LPS or DFX-induced cytokine production in peripheral mononuclear cells of cerebral infarction patients.

The Danchunwhangagam (DCWGG) has long been used for various cerebrovascular diseases. However, little scientific investigation has been carried out. Cytokines involved in the regulation of inflammatory reactions and immune responses may play a role in the pathogenesis of cerebral infarction (CI). The aim of the present study is to investigate the effect of DCWGG on the production of proinflammatory cytokines in peripheral blood mononuclear cells (PBMCs) from CI patients. The amount of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1alpha, IL-1beta, IL-6, and IL-8 in PBMC culture supernatant was significantly increased in the lipopolysaccaride (LPS)- or desferrioxamine (DFX)-treated cells compared with unstimulated cells. We showed that DCWGG inhibited the production of TNF-alpha, IL-1alpha, IL-1beta IL-6, and IL-8 induced by LPS in a dose-dependent manner. Also, DCWGG inhibited TNF-alpha, IL-1alpha, IL-beta, IL-6, and IL-8 production-induced DFX in dose-dependent manner. These results suggest that DCWGG might have regulatory effects on LPS- or DFX-induced cytokine production, which might explain its beneficial effect in the treatment of CI.